One of many research initiatives in assistant professor Rick Matthews' lab focuses on the role of extracellular matrix and cell surface glycoproteins in the developing nervous system and in learning, memory, plasticity and diseases. This slide shows extracellular matrix (ECM) staining on a glioma initiating cell.

Education & Fellowships

Previous Appointments

Research Interests

The signal transduction events that regulate the functional organization of neurons in the brain, and the phenotypes caused by defects in the genes that encode these signaling molecules.

Publications

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Research Abstract

Brain development is an exquisitely regulated phenomenon, whereby waves of differentiation produce diverse classes of neurons, oligodendrocytes and finally, astrocytes. Ultimately these cells, particularly the neurons, organize into functional networks that receive, integrate and transmit information. My lab studies how molecular signaling regulates the migration of neurons from their site of origin to destinations where they extend processes, form synapses and integrate into networks. One of our focuses is to investigate how the Reelin signaling pathway influences the positioning of distinct neuronal classes into stereotypical layers in the brain. Reelin, a secreted ligand, induces the tyrosine phosphorylation of the intracellular docking protein Dab1 by clustering the neuronal receptors ApoER2 and VLDLR and activating Src-family kinases. The tyrosine phosphorylation of Dab1 generates signaling complexes that includes the molecules Nckbeta, Crk, CrkL and PI3K. These complexes regulate the behavior of neurons as they migrate, enabling them to settle into layers. We have recently shown that Reelin signaling influences the extension of the Golgi apparatus into neuronal dendrites and the ability of neurons to polarize. We are currently investigating how these cellular behaviors influence neuronal positioning and other neuronal properties regulated by Reelin signaling.

My lab is also focused on genetic modifiers of the Reelin signaling pathway that participate in Tau phosphorylation. Tau is hyperphosphorylated in Alzheimer's and other neurological diseases and leads to the formation of neurofibrillary tangles, ultimately leading to synaptic dysfunction and neuronal death. In Reelin pathway mutants, Tau is phosphorylated in a mouse strain-dependent manner. We took advantage of this phenotype to identify Stk25 as a modifier of Reelin signaling. We found that in addition to influencing Tau phosphorylation, Stk25 regulates Golgi morphology and neuronal polarization. It interacts with the Golgi matrix protein GM130 and the LKB1-STRAD pathway. Stk25 links the LKB1-STRAD pathway, which is known to regulate cell polarization, to changes in Golgi apparatus morphology and positioning during neuronal development. We are currently investigating how Stk25 converges with the Reelin-Dab1 signaling pathway to regulate brain development. These studies have promise for understanding developmental as well as neurodegenerative diseases.